How the Structure of Per- and Polyfluoroalkyl Substances (PFAS) Influences Their Binding Potency to the Peroxisome Proliferator-Activated and Thyroid Hormone Receptors-An In Silico Screening Study

In this study, we investigated PFAS (per- and polyfluoroalkyl substances) binding potencies to nuclear hormone receptors (NHRs): peroxisome proliferator-activated receptors (PPARs) α, β, and γ and thyroid hormone receptors (TRs) α and β. We have simulated the docking scores of 43 perfluoroalkyl comp...

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Bibliographic Details
Published in:Molecules (Basel, Switzerland) Switzerland), 2023-01, Vol.28 (2), p.479
Main Authors: Kowalska, Dominika, Sosnowska, Anita, Bulawska, Natalia, Stępnik, Maciej, Besselink, Harrie, Behnisch, Peter, Puzyn, Tomasz
Format: Article
Language:English
Subjects:
Atomic properties
Binding
Chain branching
Chains
Chemicals
Fatty acids
Fluorine
Fluorocarbons - chemistry
Hormones
Metabolism
MLR
Nuclear receptors
Perfluoroalkyl & polyfluoroalkyl substances
perfluoroalkyl compounds
peroxisome proliferator-activated receptor
Peroxisome proliferator-activated receptors
Peroxisome Proliferators
PFAS
QSAR
Quantitative Structure-Activity Relationship
Receptors, Thyroid Hormone
Structure-activity relationships
Thyroid gland
Thyroid hormone receptors
thyroid receptor
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Summary:In this study, we investigated PFAS (per- and polyfluoroalkyl substances) binding potencies to nuclear hormone receptors (NHRs): peroxisome proliferator-activated receptors (PPARs) α, β, and γ and thyroid hormone receptors (TRs) α and β. We have simulated the docking scores of 43 perfluoroalkyl compounds and based on these data developed QSAR (Quantitative Structure-Activity Relationship) models for predicting the binding probability to five receptors. In the next step, we implemented the developed QSAR models for the screening approach of a large group of compounds (4464) from the NORMAN Database. The in silico analyses indicated that the probability of PFAS binding to the receptors depends on the chain length, the number of fluorine atoms, and the number of branches in the molecule. According to the findings, the considered PFAS group bind to the PPARα, β, and γ only with low or moderate probability, while in the case of TR α and β it is similar except that those chemicals with longer chains show a moderately high probability of binding.
ISSN:1420-3049
1420-3049
DOI:10.3390/molecules28020479